Previous HGNC Symbols for TNF Gene

Previous GeneCards Identifiers for TNF Gene

Summaries for TNF Gene

Entrez Gene Summary for TNF Gene

This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer. Knockout studies in mice also suggested the neuroprotective function of this cytokine. [provided by RefSeq, Jul 2008]

UniProtKB/Swiss-Prot for TNF Gene

Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key Ser-418 residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208).

The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.

Tocris Summary for TNF Gene

NF-kappaB (nuclear factor-kappa B) is a rapidly acting primary transcription factor found in all cell types. It is involved in cellular responses to stimuli such as cytokines and stress and plays a key role in regulating the immune response to infection. In unstimulated cells NF-kappaB dimers are sequestered inactively in the cytoplasm by a protein complex called inhibitor of kappa B (IkappaB). IkappaB inactivates NF-kappaB by masking the nuclear localization signals (NLS). Activation of NF-kappaB occurs via degradation of IkappaB, a process that is initiated by its phosphorylation by IkappaB kinase (IKK). Phosphorylated IkappaB becomes dissociated from NF-kappaB, unmasking the NLS. Phosphorylation also results in IkappaB ubiquitination and targeting to the proteasome. NF-kappaB can now enter the nucleus and regulate gene expression. NF-kappaB turns on expression of IkappaB forming a negative feedback loop.

The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form is further proteolytically processed by SPPL2A or SPPL2B through regulated intramembrane proteolysis producing TNF intracellular domains (ICD1 and ICD2) released in the cytosol and TNF C-domain 1 and C-domain 2 secreted into the extracellular space.

UniProtKB/Swiss-Prot Function: Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key Ser-418 residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208).

Pomalidomide, previously known as CC-4047 or actimid, is a potent immunomodulatory molecule that exhibits antineoplastic activity for the treatment of hematological malignancies, especially relapsed and refractory multiple myeloma (MM).

UniProtKB/Swiss-Prot

Psoriatic arthritis (PSORAS) [MIM:607507]: An inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoid like pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis). {ECO:0000269 PubMed:12746914}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.